Withdrawal from Chronic Phencyclidine Treatment Induces Long-Lasting Depression in Brain Reward Function

Abstract

Phencyclidine (PCP) is a drug of abuse that has rewarding and dysphoric effects in humans. The complex actions of PCP, and PCP withdrawal in particular, on brain reward function remain unclear. The purpose of the present study was to characterize the effects of withdrawal from acute and chronic PCP treatment on brain reward function in rats. A brain stimulation reward procedure was used to evaluate the effects of acute PCP injection (0, 5, or 10 mg/kg) or chronic PCP treatment (0, 10, 15, or 20 mg/kg/day for 14 days delivered via subcutaneous osmotic minipumps) on brain reward function. Withdrawal from acute administration of 5 and 10 mg/kg PCP produced a decrease in brain reward function as indicated by a sustained elevation in brain reward thresholds. When administered chronically, 10, 15, or 20 mg/kg/day PCP induced a progressive dose-dependent potentiation of brain stimulation reward, while cessation of the treatment resulted in significant elevations in reward thresholds reflecting diminished reward. Specifically, withdrawal from 15 or 20 mg/ kg/day PCP induced a depression in brain reward function that lasted for the entire month of observation. These results indicate that prolonged continuous administration of high PCP doses facilitates brain stimulation reward, while withdrawal from acute high PCP doses or chronic PCP treatment results in a protracted depression of brain reward function that may be analogous to the dysphoric and anhedonic symptoms observed in PCP dependence, depression, and schizophrenia.

Progressive ratio performance following challenge with antipsychotics, amphetamine, or NMDA antagonists in adult rats treated perinatally with phencyclidine

“…These results are consistent with those of a previous study in which dizocilpine only minimally affected breakpoints for food reinforcement in rhesus monkeys (Buffalo et al 1994). Further, acute dosing with PCP did not alter responding for intracranial brain stimulation (Spielewoy and Markou 2003), nor did it decrease voluntary sucrose consumption within a few hours after administration (Turgeon and Hoge 2003). Rather, effects on responding for brain stimulation and sucrose consumption were delayed and may have been associated with withdrawal from PCP.…”

Analysis of licking microstructure provides no evidence for a reduction in reward value following acute or sub-chronic phencyclidine administration

“…There is some evidence that withdrawal from chronic PCP treatment using higher doses can produce anhedonic effects using an intracranial self-stimulation paradigm (Spielewoy and Markou 2003). However, since such high doses are known to cause pathology that is not produced in schizophrenia (e.g.…”

Personality measures in former heroin users receiving methadone or in protracted abstinence from opiates

“…Moreover, the fact that elevated schizophrenia-spectrum traits are found in subjects 6-18 months after discontinuation from MMT suggests that methadone discontinuation may result in a protracted opiate withdrawal syndrome (42,43). Protracted withdrawal syndromes were also found in studies of phencyclidine (PCP) (44) and alcohol (45) addiction and may influence vulnerability to relapse.…”